Objectives: 1) Determine the risk of transfusion-transmitted hepatitis C virus (HCV) in cardiac surgery patients before and after donor screening for anti-HCV and surrogate markers of non-A, non-B hepatitis (NANBH). 2) To characterize donors who are HCV seronegative and who lacked surrogate markers at the time of donation, but whose recipient seroconverted to HCV. Population: Cardiac surgery patients enrolled in an ongoing investigation of the effectiveness of HIV-1 screening of blood donors constitute the study population. Three hospitals contribute patients to this study; Johns Hopkins Hospital, Baltimore, and two in Houston. Samples are available from 1,062 patients who underwent surgery before surrogate screening was implemented to prevent NANBH, 8,661 samples are from patients after surrogate screening began, and over 2,700 samples from patients screened for both anti-HCV and surrogate markers. Methods: This is a nonconcurrent prospective, seroepidemiologic study. To estimate the incidence of HCV infection, 6-month postoperative serum samples will be tested for antibody to HCV. Preoperative samples corresponding to positive postoperative sera will also be tested. The donors of a patient who has received blood screened for HCV, i.e., a donation since May, 1990, and seroconverted in the six months since transfusion will be located and retested for antibodies to HCV. The donors will be administered a questionnaire designed to ascertain risk factors for HCV infection. A sample of donors who were HCV positive at the time of donation will be given the same questionnaire. Comparison of these 3 groups of donors (i.e., seropositives, donors tested negative but implicated in seroconversion, seronegatives) will allow an investigation of factors which are associated with false negative screening results. Analytical methods will include standard methods for contingency tables and both conditional and unconditional logistic regression. Significance: Posttransfusion NANBH, mainly caused by HCV, is the most common serious complication of transfusions, occurring in 2-5% of transfusion recipients. About 50% of those infected develop chronic hepatitis, of whom, 10%-20% develop cirrhosis. Hepatocellular carcinoma has been reported to occur in some. This study will provide the first evaluation of the effectiveness of donor screening for anti-HCV by the recently licensed HCV antibody test and surrogate markers of NANBH. It will also provide a precise estimate of the risk of transfusion-transmitted HCV. Our results should allow examination of risk factors for HCV infected donors who are seronegative at the time of donation.